Senescent fibroblast facilitates re-epithelization and collagen deposition in radiation-induced skin injury through IL-33-mediated macrophage polarization.

BACKGROUND: The need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues. However, the effects and mechanisms of senescent cells on re-epithelialization and collagen deposition in radiation-induced skin injury have not been fully elucidated. RESULTS: Here, we identified a role for a population of senescent cells expressing p16 in promoting re-epithelialization and collagen deposition in radiation-induced skin injury. Targeted ablation of p16+ senescent cells or treatment with Senolytics resulted in the disruption of collagen structure and the retardation of epidermal coverage. By analyzing a publicly available single-cell sequencing dataset, we identified fibroblasts as a major contributor to the promotion of re-epithelialization and collagen deposition in senescent cells. Notably, our analysis of publicly available transcriptome sequencing data highlighted IL-33 as a key senescence-associated secretory phenotype produced by senescent fibroblasts. Neutralizing IL-33 significantly impedes the healing process. Finally, we found that the effect of IL-33 was partly due to the modulation of macrophage polarization. CONCLUSIONS: In conclusion, our data suggested that senescent fibroblasts accumulated in radiation-induced skin injury sites participated in wound healing mainly by secreting IL-33. This secretion regulated the local immune microenvironment and macrophage polarization, thus emphasizing the importance of precise regulation of senescent cells in a phased manner.

Identification and characterization of an angiotensin-converting enzyme inhibitory peptide derived from bovine casein.

In this study, we identified a novel angiotensin-I-converting enzyme (ACE) inhibitory peptide, YQKFPQYLQY (YQK), derived from bovine casein. Casein was hydrolyzed using pepsin and trypsin. The target peptide, YQK, was separated from the hydrolysate by ultrafiltration and Sephadex G-15chromatography. The IC50 value of YQK was 11.1µM. YQK retained its ACE inhibitory activity under various temperature and pH conditions. It was also stable against the digestive enzymes pepsin and trypsin. The Lineweaver-Burk plot suggested that the inhibitory mode of YQK was competitive. Furthermore, its antihypertensive effects in spontaneously hypertensive rats (SHRs) also revealed that oral administration of YQK can significantly decrease systolic blood pressure. These results suggested that YQK may have potential applications in functional foods or pharmaceuticals as an antihypertensive agent.

[Relationship between the Trypsin Activity and Conformational Change Caused by Ultra High Static Pressure].

Trypsin was treated by high pressure technology, and its spatial structure was changed, the relationship between structural changes and trypsin activity was investigated. The secondary structure change of trypsin after pressure treatment was observed by Fourier transform infrared spectroscopy(FTIR). Moreover its tertiary structure change was observed by fluorescence spectroscopy; and its activity was tested using Folin phenol method. The results showed that, compared with the untreated(0.1 MPa), trypsin activity change was significant(p<0. 05) under different pressure(100~600 MPa) treatment at 37 °C for 20 min. After treated with 300 MPa, its activity was 0. 386 times higher than the untreated. Secondary structure of trypsin was analysed using FTIR, and the peak area ratio of α-helix and ß-tum in secondary structure was the maximum(2. 749); Endogenous fluorescence spectra intensity was the maximum (1 353) at excitation wavelength 295 nm, and was 4 262 at excitation wavelength 280 nm; exogenous fluorescent spectra intensity was 2 022 at excitation wavelength 228 nm, all these change was remarkable(p<0. 05) comparing with the untreated. Therefore, ultrahigh pressure processing influence on the spatial structure of trypsin and induce enzyme activity.change. Trypsin activity is relate to the peak area ratio of α-helix and ß-turn and the exposure degree of Trp and other hydrophobic a mino acid residues and Tyr.

Human FcRn can mediate the transport across intestinal mucosal barrier and prolong the half-life of rabbit IgG in vivo

FcRn (neonatal Fc receptor) plays an important role in IgG transportation, antigen presentation and signal transmission. In this study, the complement fixation test and flow cytometry test were performed to verify whether the heterologous antibody could be transmitted to the serum or leukocyte with FcγR (Fc gamma receptor) across the intestinal mucosa. The results showed that rabbit anti-bovine IgG could be detected in both the serum and the leukocytes, which indicated that the heterologous antibody could transport across the intestinal mucosa to enter the blood and be effectively delivered to the leukocytes with FcγR. In addition, the results also showed that the rabbit anti-bovine IgG still could be detected in the leukocyte group (P=0.044<0.05) after 21 days. It indicated that the rabbit IgG could exist in the body for a long term (up to 21 days) after being transported to the cells containing FcγR.